chr12-102479459-G-C

Variant names:

• chr12-102479459-G-C
• rs5742614
• NM_000618.5:c.63+860C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000618.5(IGF1):​c.63+860C>G variant causes a intron change. The variant allele was found at a frequency of 0.0408 in 152,184 control chromosomes in the GnomAD database, including 369 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.041 (369 hom., cov: 32)
• Consequence: IGF1 NM_000618.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20
• Publications: 3 publications found

Genes affected

IGF1 (HGNC:5464): (insulin like growth factor 1) The protein encoded by this gene is similar to insulin in function and structure and is a member of a family of proteins involved in mediating growth and development. The encoded protein is processed from a precursor, bound by a specific receptor, and secreted. Defects in this gene are a cause of insulin-like growth factor I deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate mature protein. [provided by RefSeq, Sep 2015]

LINC02456 (HGNC:53389): (long intergenic non-protein coding RNA 2456)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000618.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	NM_000618.5	MANE Select	c.63+860C>G		intron	N/A	NP_000609.1	Q5U743
	IGF1	NM_001111285.3		c.63+860C>G		intron	N/A	NP_001104755.1	P05019-1
	IGF1	NM_001414005.1		c.63+860C>G		intron	N/A	NP_001400934.1	P05019-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF1	ENST00000337514.11	TSL:1 MANE Select	c.63+860C>G		intron	N/A	ENSP00000337612.7	P05019-2
	IGF1	ENST00000307046.8	TSL:1	c.63+860C>G		intron	N/A	ENSP00000302665.8	P05019-1
	IGF1	ENST00000392904.5	TSL:5	c.63+860C>G		intron	N/A	ENSP00000376637.1	P05019-4

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6191 AN: 152068 Hom.: 370 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0116

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00447

Gnomad OTH AF: 0.0377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0408 AC: 6202 AN: 152184 Hom.: 369 Cov.: 32 AF XY: 0.0394 AC XY: 2929 AN XY: 74400

African (AFR) AF: 0.129 AC: 5362 AN: 41496

American (AMR) AF: 0.0176 AC: 269 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4814

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10594

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00447 AC: 304 AN: 68020

Other (OTH) AF: 0.0373 AC: 79 AN: 2116

Alfa AF: 0.000833 Hom.: 0

Bravo AF: 0.0448

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		5.2
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5742614; hg19: chr12-102873237;